Safety and Pharmacokinetics of Sialic Acid Tables in Patients With Hereditary Inclusion Body Myopathy (HIBM)

Ultragenyx

Status and phase

Completed

Phase 1

Conditions

Hereditary Inclusion Body Myopathy (HIBM)

Treatments

Drug: Sialic Acid Extended Release (SA-ER) Tables

Drug: Sialic Acid Extended Release (SA-ER) Tablets

Study type

Interventional

Funder types

Industry

Identifiers

NCT01359319

UX001-CL101

Details and patient eligibility

About

Hereditary Inclusion Body Myopathy (HIBM) is a severe progressive metabolic myopathy caused by a defect in the biosynthetic pathway for sialic acid (SA), a critical component of many muscle proteins, resulting in a deficiency in SA in the muscles of HIBM patients.

The effective replacement of the missing SA substrate is theoretically simple, and, in animal models, replacement with SA showed significant restoration of sialylation biochemistry and excellent reduction in muscle disease. These data show that replacement can achieve significant clinical benefit in muscle pathology, function, and survival.

Enrollment

26 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Must be 18 years to 70 years of age.
Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures.
Must have a documented diagnosis, confirmed by genetic testing, of hereditary inclusion body myopathy (HIBM), also known as distal myopathy, rimmed vacuoles (DMRV), or Nonaka myopathy due to demonstrated mutations in gene encoding the GNE/MNK enzyme.
Willing and able to comply with all study procedures, including multiple overnight stays at a hospital unit or Phase 1 unit.
Sexually active subjects must be willing to use an acceptable method of contraception (i.e double barrier method)while participating in the study and for 30 days after receiving the last dose of SA-ER.
Females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had bilateral tubal ligation at least 1 year prior to screening, or who have had total hysterectomy.

Exclusion criteria

Pregnant or breastfeeding at screening or planning to become pregnant (self or partner) at any time during the study.
Use of any investigational product or investigational medical device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
Ingestion of ManNAc, sialic acid, or related metabolites or sialic acid donors that provide this substrate in either chemical or nutritional supplement form during the 30 days prior to screening. If ManNAc or other substrate was used more than 30 days prior to screening, the time period of use, the compound used, and the dose and dose regimen should be recorded in the patient's history. If a patient has been on substrate replacement therapy in the past, the investigator must consider the potential confounding effects of this therapy before enrolling the patient.
Presence of a condition the severity and acuity of which, in the opinion of the investigator, warrant immediate surgical intervention or other treatment.
Presence or history of any hypersensitivity to SA or its excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects.
Presence of a concurrent disease or condition that would interfere with study participation or affect safety such as swallowing difficulties.
Presence or history of any condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study.
Serum transaminase (ALT, AST, GGT) levels > 3 x upper limit of normal (ULN) or serum creatinine > 2.0 mg/dL.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Single Group Assignment

Masking

None (Open label)

26 participants in 5 patient groups

650 mg (single dose only)

Experimental group

Description:

Each patient will be sequentially assigned to a specific dose level and will receive two single-dose exposures at that same dose level (fasted and fed). The low-dose cohorts will be filled before assigning higher-dose cohorts. The patient will then be assigned to receive one repeat-dose regimen. The lower-dose repeat-dose cohorts will be filled before proceeding to higher repeat-dose levels.

Treatment:

Drug: Sialic Acid Extended Release (SA-ER) Tablets

1,950 mg (single and repeat dose)

Experimental group

Description:

Treatment:

Drug: Sialic Acid Extended Release (SA-ER) Tables

2,925 mg (single and repeat dose)

Experimental group

Description:

Treatment:

Drug: Sialic Acid Extended Release (SA-ER) Tablets